Experimental therapies under investigation for COVID-19.

Coronavirus Disease 2019, caused by the virus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), is a pandemic first discovered in Wuhan, China which has claimed over 1.7 million lives to date across the globe as of 24 December 2020. As the virus spreads across the world affecting millions of patients, there has been a massive movement to discover readily available and effective treatment options including vaccines. One of the limiting factors in treating the disease is its varied presentation and effect in patients, ranging from asymptomatic patients to those left in intensive care units, intubated and fighting for their lives. There are numerous clinical trials and small-scale studies underway to investigate potential treatment options. However, very few studies and drugs demonstrated efficacy while many more are under investigation, leaving care teams dependent on supportive care coupled with experimental treatment options. In this review, we summarize the various treatment options explored to treat COVID-19, discussing possible the mechanisms of fighting the virus.

Levels of 25-hydroxy Vitamin D3 and Vitamin D Receptor Polymorphism in Severe Dengue Cases from New Delhi.

BACKGROUND: Dengue is the "phoenix" that never went to ashes. First identified in 1943, in Japan, dengue virus has worldwide distribution and is a grave public health concern in developing countries like India; Methods: A cross sectional study was conducted among adults suspected of having dengue fever and attending Lok Nayak Hospital, New Delhi. Restriction Fragment Length Polymorphism was completed for the detection of vitamin D receptor (VDR) gene polymorphism; Results: Serum 25-hydroxy vitamin D3 (vitamin D) levels were found to be 1.6 times elevated in severe dengue cases as compared to healthy controls. Vitamin D levels were significantly higher in secondary infections compared to primary infections as well as secondary severe dengue cases as compared to secondary non-severe cases (p value < 0.05). A significant association of the T allele (rs2228570) was seen in severe dengue cases, while, when comparing the A/A with A/C and C/C genotypes (rs7975232) among dengue cases and healthy controls, the odds ratio was estimated to be 1.24 (0.55-2.75, p > 0.05) and 0.28 (0.08-0.96, p < 0.05) respectively; Conclusions: The present study is an attempt at decoding the role of vitamin D in dengue disease pathogenesis and exploring the role of genetic polymorphism in dengue disease pathogenesis.

Moderate noise associated oxidative stress with concomitant memory impairment, neuro-inflammation and neurodegeneration.

Noise, a disturbing and unwanted sound is currently being perceived as a widespread environmental stressor. In the present study we investigated the activation of oxidative stress as a mechanism involved in cognitive impairment through changes in neuro-inflammation. Sprague Dawley rats (200-220 â€‹ â€‹g â€‹m) were exposed to moderate (100dB) sound pressure level (SPL) noise daily for 2 â€‹h â€‹s over a period of 15 and 30 days and the consequence on brain regions of hippocampus observed through behavioral studies by Morris Water Maze to assess effects on spatial memory coupled with biochemical evaluation of markers of oxidative stress and inflammation. Further, the underlying mechanism pertaining to apoptosis was investigated by immuno-histological studies through assessment of Caspase-3 and TUNEL assay as well as morphological parameters, namely Nissl bodies in CA1, CA3 and DG regions of hippocampus. Poorer performance in the MWM indicative of decrement in concept formation, attention, working memory, and reference memory was observed on 15 and 30 days of noise exposures. At the cellular level, increased oxidative stress and inflammation was noticed as evinced by elevated levels of TNF-α, IL-6, IL-1α and IFN-γ in both hippocampus and plasma. Exposure to noise also led to a gradual increase in the number of pyknotic and apoptotic neurons together with the increase in DNA fragmentation in hippocampus. Increased levels of inflammatory genes (i.g.) ccl2, ccr5, ifng, il13, il1a, tnfa coupled with decreased levels of bmp2 and il3 genes were found in both the noise exposure groups. Our findings revealed that moderate intensity noise exposure impaired early memory changes in expression of several gene families including genes associated with regulation of transcription, inflammatory response, and, response to oxidative stress.

Attenuation of adverse effects of noise induced hearing loss on adult neurogenesis and memory in rats by intervention with Adenosine A2A receptor agonist.

Hearing loss and cognitive decline are commonly associated with aging and morbidity. Present clinical interest lies in whether peripheral hearing loss promotes cognitive decline and if prophylaxis with selective adenosine receptor agonist CGS21680 effectively mitigates the adverse effects. In the current study, male Sprague Dawley rats weighing 200-250 g m were randomly allocated into three groups: Group 1) rats exposed to 100 dB SPL white noise, 2 h a day for 15 consecutive days, 2) rats supplemented with an adenosine receptor agonist, CGS21680 at 100 µg/kg/day prior to noise exposure and 3) unexposed control rats. Baseline hearing and cognition assessed by auditory brainstem response (ABR) and water maze respectively was undertaken for all the groups. Phalloidin stain and synaptic ribbons count in cochlea, and, Ki67, DCX and NeuN in hippocampus were observed by immunohistochemistry. It was inferred that noise exposed rats showed elevated thresholds of ABR and poorer performances in spatial working memory when compared with controls. On the contrary, CGS21680 administered group exhibited improved ABR and cognitive functions with shorter mean latency and path-length to reach the platform, significant reduction in the noise induced loss of synaptic ribbons count and increased number of Ki67 and doublecortin (DCX) positive cells compared to their noise exposed counterparts. Pharmacologic intervention with selective A2A receptor agonist CGS21680 provided adequate protection from noise by effectively maintaining hearing threshold levels, cell viability in cochlea and hippocampus & functional/intact reference memory.

Distortion product oto-acoustic emission: a superior tool for hearing assessment than pure tone audiometry.

OBJECTIVE: Hearing plays a crucial role in the performance of a soldier and is important for communication and speech processing. Service personnel are constantly exposed to high levels of noise and hence predisposed to occupational health disabilities, principally noise-induced hearing loss (NIHL) and tinnitus. NIHL is a significantly common impairment in the military and can affect the warfare performances. Parochial awareness about the effects of uproarious noise which exacerbates their hearing, acceptance rate of use of hearing protection devices and follow-up audiological tests have become the major drawback for prevention of NIHL and are less pondered upon. METHOD: The present study focuses on the effects of noise on the hearing of service crew operating and maintaining military equipment and explores the efficacy of DPOAE's to substitute pure tone audiometry as a quick, easy to operate and implementable test technique for monitoring of hearing status. RESULTS: The results suggest that DPOAE test is important and more coherent than audiometry alone for the early detection of cochlear injury due to noise from military operations and efficacious for detecting NIHL.

Occupational EMF exposure from radar at X and Ku frequency band and plasma catecholamine levels.

Workers in certain occupations such as the military may be exposed to technical radiofrequency radiation exposure above current limits, which may pose a health risk. The present investigation intended to find the effect of chronic electromagnetic field (EMF) exposure from radar on plasma catecholamines in the military workforce. In the study, 166 male personnel selected randomly were categorized into three groups: control (n = 68), exposure group-I (X-band, 8-12 GHz, n = 40), and exposure group-II (Ku-band, 12.5-18 GHz, n = 58). The three clusters were further divided into two groups according to their years of service (YOS) (up to 9 years and ≥10 years) to study the effect of years of radar exposure. Enzyme immunoassay was employed to assess catecholamine concentrations. EMF levels were recorded at different occupational distances from radar. Significant adrenaline diminution was registered in exposure group-II with no significant difference in exposure group-I when both groups were weighed against control. Nor-adrenaline and dopamine levels did not vary significantly in both exposure groups when compared to controls. Exposure in terms of YOS also did not yield any significant alteration in any of the catecholamines and in any of the exposure groups when compared with their respective control groups. The shift from baseline catecholamine values due to stress has immense significance for health and well-being. Their continual alteration may prove harmful in due course. Suitable follow-up studies are needed to further strengthen these preliminary observations and for now, exposures should be limited as much as possible with essential safeguards.

Effect of occupational EMF exposure from radar at two different frequency bands on plasma melatonin and serotonin levels.

OBJECTIVE: To delineate the effect of chronic electromagnetic field (EMF) exposure from radar on plasma melatonin and serotonin levels in occupationally exposed military personnel. SUBJECTS AND METHODS: A total of 166 male military personnel participated in the study out of which only 155 joined for blood draw. They were divided into three sets: Control group (n = 68), exposure group I (n = 40) exposed to 8-12 GHz and exposure group II (n = 58) working with radar at 12.5-18 GHz frequency. The three groups were further split into two groups according to their years of service (up to 10 years and > 10 years) in order to investigate the effect of years of exposure from radar. Melatonin and serotonin levels were estimated by enzyme immunoassay in fasting blood samples collected from 06:00-07:00 h. EMF measurements were recorded at different locations using Satimo EME Guard 'Personal Exposure Meter' and Narda 'Broad Band Field Meter'. RESULTS: The group I exposed population registered a minor though not significant decrease in plasma melatonin concentration while the other group II exposed population registered statistically significant decline in melatonin concentration when compared with controls. Highly significant increase in plasma serotonin levels was found in exposure group II when compared to control whereas marginal non-significant rise was also registered in exposure group I in comparison to control. Exposure in terms of length of service up to 10 years did not produce any significant effect in the indoleamine levels in both the exposure groups when they were compared with their respective control groups. Whereas, length of service greater than 10 years was observed to decrease and increase respectively the melatonin and serotonin concentration significantly in exposure group II but not in exposure group I. However, correlation test did not yield any significant association between years of service and melatonin or serotonin levels respectively in both the exposure sets I and II. No significant association was observed between melatonin and serotonin levels as well. CONCLUSION: The study showed the EMF ability to influence plasma melatonin and serotonin concentration in radar workers, significantly in 12.5-18 GHz range with service period greater than 10 years.

Effect of vitamin E supplementation on carbogen-induced amelioration of noise induced hearing loss in man.

The study explores the effect of occupational noise on oxidative stress status and prophylactic effect of Vitamin E and carbogen (5% CO 2 +95%O 2 ) breathing in alleviating the oxidative damage and conserving the hearing in human volunteers exposed to intense occupational noise. Plasma total antioxidant status, blood glutathione (GSH), malondialdehyde (MDA), antioxidant enzyme activities of GSH peroxidase (EC 1.11.1.9, GPx), superoxide dismutase (EC 1.15.1.1; SOD) in erythrocytes, nitric oxide and nitric oxide synthase in plasma were assessed before and after 6 days of administration of Vitamin E and Carbogen. Results of the study indicate that the exposure to noise for 6 days increased blood concentration of MDA, decreased concentrations of reduced GSH, antioxidant enzyme activity of SOD and plasma total antioxidant status in control (noise) group. Vitamin E- supplemented group showed decline in oxidative stress reflected by significant decrease in blood concentration of MDA and increase in antioxidant enzyme activity of erythrocyte SOD. Results of audiometric studies revealed that breathing of carbogen prevented the development of temporary threshold shift; thereby reducing the risk of noise induced hearing loss.